Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Accession Number
DB01075  (APRD00587, DB06975)
Small Molecule
Approved, Investigational

Diphenhydramine - perhaps known most commonly as its brand name formulation Benadryl - is a first-generation H1 receptor antihistamine that is used extensively for the treatment of seasonal allergies, insect bites and stings, and rashes 9,10,11,15. However, it also has antiemetic, antitussive, hypnotic, and antiparkinson properties 11,14. As histamine receptors exist both peripherally and in the central nervous system, diphenhydramine has been shown to cause sedation due to its competitive antagonism of histamine H1 receptors within the central nervous system 9,10,11,15,5. While its use in allergy therapy can sometimes fall out of favor due to its sedative effect, diphenhydramine has been repurposed for use within many non-prescription over-the-counter sleep aids and cough-and-cold medications that have been marketed for "night time" use 9,12,13.

Diphenhydramine is also used in combination with 8-chlorotheophylline as the anti-nausea drug Dimenhydrinate where it is utilized primarily for its antagonism of H1 histamine receptors within the vestibular system 4.

Diphenhydramine has also been shown to be implicated in a number of neurotransmitter systems that affect behaviour including dopamine, norepinephrine, serotonin, acetylcholine, and opioid 3. As a result, diphenhydramine is being investigated for its anxiolytic and anti-depressant properties.

  • 2-(benzhydryloxy)-N,N-dimethylethylamine
  • 2-diphenylmethoxy-N,N-demthylethanamine
  • Difenhidramina
  • Diphenhydramine
  • Diphenhydraminum
  • N-(2-(diphenylmethoxy)ethyl)-N,N-dimethylamine
  • O-benzhydryldimethylaminoethanol
  • α-(2-dimethylaminoethoxy)diphenylmethane
  • β-dimethylaminoethanol diphenylmethyl ether
  • β-dimethylaminoethyl benzhydryl ether
Product Ingredients
IngredientUNIICASInChI Key
Diphenhydramine citrate4OD433S20988637-37-0SPCKHVPPRJWQRZ-UHFFFAOYSA-N
Diphenhydramine hydrochlorideTC2D6JAD40147-24-0PCHPORCSPXIHLZ-UHFFFAOYSA-N
Diphenhydramine methylbromideUJO67AO8YI31065-89-1BDQPXVWYFLTETB-UHFFFAOYSA-M
Diphenhydramine salicylate707L3YC54L7491-10-3RTSZUSOHOIFYSY-UHFFFAOYSA-N
Active Moieties
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BenadrylInjection, solution50 mg/1mLIntramuscular; IntravenousParke Davis Div Of Pfizer Inc1947-03-062008-01-31Us
BenadrylInjection, solution50 mg/1mLIntramuscular; IntravenousPhysicians Total Care, Inc.1994-06-012010-12-29Us
BenadrylInjection, solution50 mg/1mLIntramuscular; IntravenousPhysicians Total Care, Inc.2006-01-132010-12-29Us
BenadrylInjection, solution50 mg/1mLIntramuscular; IntravenousParke Davis Div Of Pfizer Inc1957-12-302007-01-31Us
Benadryl Inj. 50mg/mlLiquid50 mgIntramuscular; IntravenousWarner Lambert Canada Inc.1994-12-312000-11-27Canada
DicopanolKit0.86 g/0.86gOralCalifornia Pharmaceuticals, Llc2016-01-01Not applicableUs
DicopanolKit0.75 g/0.75gOralFusion Pharmaceuticals LLC2010-02-08Not applicableUs
Diphenhydramine HCl Inj USP 50mg/mlLiquid50 mgIntravenousInternational Medication Systems, Limited1974-12-311997-08-15Canada
Diphenhydramine HCl Injection, USPSolution50 mgIntramuscular; IntravenousSterimax Inc1994-12-31Not applicableCanada
Diphenhydramine Hydrochloride InjectionSolution50 mgIntramuscular; IntravenousFresenius Kabi2012-02-17Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Diphendydramine HydrochlorideCapsule25 mg/1OralRemedy Repack2010-12-172017-04-24Us66424 0020 01 nlmimage10 1a038d6c
DiphenhydramineInjection, solution50 mg/1mLIntravenousRemedy Repack2013-11-182017-01-20Us
DiphenhydramineInjection, solution50 mg/1mLIntramuscular; IntravenousMicro Labs Limited2018-12-04Not applicableUs
DiphenhydramineInjection, solution50 mg/1mLIntramuscular; IntravenousFresenius Kabi USA, LLC2002-08-01Not applicableUs
Diphenhydramine HciInjection, solution50 mg/1mLIntramuscular; IntravenousHF Acquisition Co LLC, DBA HealthFirst2018-11-19Not applicableUs
Diphenhydramine HydrochlorideInjection, solution50 mg/1mLIntramuscular; IntravenousGeneral Injectables and Vaccines, Inc2017-06-13Not applicableUs
Diphenhydramine HydrochlorideInjection, solution50 mg/1mLIntramuscular; IntravenousCardinal Health1988-11-20Not applicableUs
Diphenhydramine HydrochlorideCapsule50 mg/1OralRemedy Repack2013-03-252014-03-25Us
Diphenhydramine HydrochlorideInjection, solution50 mg/1mLIntramuscular; IntravenousHF Acquisition Co LLC, DBA HealthFirst2018-11-26Not applicableUs
Diphenhydramine HydrochlorideCapsule50 mg/1OralPreferreed Pharmaceuticals Inc.2010-12-132013-03-27Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
7 Select AllergyTablet25 mg/1Oral7 Eleven2014-04-22Not applicableUs
7 Select Allergy ChildrensSolution12.5 mg/5mLOral7 Eleven2014-08-05Not applicableUs
7 Select Night Time Sleep AidSolution50 mg/30mLOral7 Eleven2014-04-22Not applicableUs
Adult AllergySolution50 mg/20mLOralChain Drug Consortium2015-05-04Not applicableUs
Adult Allergy ReliefSolution50 mg/20mLOralWalmart Stores2017-05-03Not applicableUs
After Bite OutdoorGel20 mg/1gTopicalTender Corporation2018-03-01Not applicableUs
After Bite OutdoorGel20 mg/1mLTopicalTender Corporation2016-11-012018-03-01Us
After Bite PlusCream20 mg/1mLTopicalTender Corporation2012-07-032018-03-06Us
After Bite PlusGel20 mg/1gTopicalTender Corporation2018-03-01Not applicableUs
After Bite XtraGel20 mg/1mLTopicalTender Corporation2016-11-012018-03-06Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
7 Select Ibuprofen PMDiphenhydramine citrate (38 mg/1) + Ibuprofen (200 mg/1)Tablet, film coatedOral7 Eleven2014-08-05Not applicableUs
7 Select Night Time Severe Cold Cough and FluDiphenhydramine hydrochloride (25 mg/1) + Acetaminophen (650 mg/1) + Phenylephrine hydrochloride (10 mg/1)Powder, for solutionOral7-Eleven2016-01-25Not applicableUs
7 Select Night Time severe cold, cough and fluDiphenhydramine hydrochloride (25 mg/1) + Acetaminophen (650 mg/1) + Phenylephrine hydrochloride (10 mg/1)Powder, for solutionOral7 Eleven2015-11-122017-08-01Us
7 Select Pain Relief PMDiphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)Tablet, film coatedOral7 Eleven2014-09-042016-07-22Us
7-Select Advil PMDiphenhydramine citrate (38 mg/1) + Ibuprofen (200 mg/1)Tablet, coatedOralLil' Drug Store Products, Inc.2011-06-012017-12-31Us
Acedif PLUSDiphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)TabletOralPlus Distributors LLC2019-02-01Not applicableUs
Aceta-gesicDiphenhydramine hydrochloride (12.5 mg/1) + Acetaminophen (325 mg/1)Tablet, coatedOralRemedy Repack2014-08-08Not applicableUs
Aceta-gesicDiphenhydramine hydrochloride (12.5 mg/1) + Acetaminophen (325 mg/1)Tablet, coatedOralRugby2014-06-30Not applicableUs
AcetadrylDiphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)Tablet, film coatedOralAidarex Pharmaceuticals LLC2011-07-21Not applicableUs
AcetadrylDiphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)Tablet, film coatedOralPhysicians Science & Nature Inc.2011-07-212016-05-31Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AiracofDiphenhydramine hydrochloride (12.5 mg/5mL) + Codeine phosphate hemihydrate (7.5 mg/5mL) + Phenylephrine hydrochloride (7.5 mg/5mL)LiquidOralCenturion Labs2010-01-082016-05-02Us
Antiphlamine Coin PlasterDiphenhydramine (0.246 mg/0.2832g) + Levomenthol (2.769 mg/0.2832g) + Synthetic camphor (1.108 mg/0.2832g)PatchTopicalHanul Trading Co., Ltd.2016-10-102017-04-14Us
Antiphlamine Coin PlasterDiphenhydramine (0.246 mg/0.2832g) + DL-alpha-Tocopherol (0.308 mg/0.2832g) + Levomenthol (2.769 mg/0.2832g) + Methyl salicylate (5.541 mg/0.2832g) + Nonivamide (0.046 mg/0.2832g) + Peppermint oil (0.693 mg/0.2832g) + Synthetic camphor (1.108 mg/0.2832g)PatchTopicalHanul Trading Co., Ltd.2016-10-10Not applicableUs
BenadrylDiphenhydramine hydrochloride (50 mg/1mL)Injection, solutionIntramuscular; IntravenousPhysicians Total Care, Inc.1994-06-012010-12-29Us
BenadrylDiphenhydramine hydrochloride (50 mg/1mL)Injection, solutionIntramuscular; IntravenousPhysicians Total Care, Inc.2006-01-132010-12-29Us
Contrast Allergy PreMed PackDiphenhydramine hydrochloride (50 mg/50mg) + Prednisone (50 mg/50mg)KitOralShertech Laboratories, Llc2016-09-13Not applicableUs
DermagesicDiphenhydramine hydrochloride (1 mg/100mL) + Phenol (1.4 mg/100mL)LiquidTopicalLlorens Pharmaceuticals International Division2009-02-012014-01-20Us
DicopanolDiphenhydramine hydrochloride (0.86 g/0.86g)KitOralCalifornia Pharmaceuticals, Llc2016-01-01Not applicableUs
DicopanolDiphenhydramine hydrochloride (0.75 g/0.75g)KitOralFusion Pharmaceuticals LLC2010-02-08Not applicableUs
Diphenhydramine HClDiphenhydramine hydrochloride (25 mg/1)TabletOralCardinal Health2011-06-032018-05-25Us
International/Other Brands
Aleryl / Alledryl / Allerdryl (Valeant) / Belix / Benylan (Biogen) / Dermodrin (Montavit) / Desentol (Meda) / Dibondrin (Montavit) / Dimedrol (Zdorovie) / Diphen (Wockhardt) / Dormarex 2 / Genahist / Histaxin (Meda) / Hyrexin (Hyrex) / Nytol Quickgels (GlaxoSmithKline) / Restamin (Kowa Souyaku) / Siladryl / Silphen Cough
CAS number
Average: 255.3547
Monoisotopic: 255.162314299
Chemical Formula
InChI Key



Diphenhydramine is a first-generation histamine H1 receptor antagonist (H1 antihistamine) that is widely available as a non-prescription, over-the-counter (OTC) medication. As an OTC medication, diphenhydramine is typically formulated as tablets and creams indicated for use in treating sneezing, runny nose, itchy/watery eyes, itching of nose or throat, insomnia, pruritis, urticaria, insect bites/stings, allergic rashes, and nausea 9,10,11,15,5.

Additionally, when the use of oral diphenhydramine is impractical, there are also prescription-only formulations such as diphenhydramine injection products that are effective in adults and pediatric patients (other than premature infants and neonates) for: i) the amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after acute allergic reaction symptoms have been controlled, and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated 14; ii) the active treatment of motion sickness 14; and iii) use in parkinsonism when oral therapy is impossible or contraindicated, as follows: parkinsonism in the elderly who are unable to tolerate more potent agents; mild cases of parkinsonism in other age groups, and in other cases of parkinsonism in combination with centrally acting anticholinergic agents 14.

Associated Conditions

Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties 12. The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone 12. Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere 12. Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone 12. Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain 12.

Mechanism of action

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors 9,10,11,15,5. Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons 9,10,11,15,5. When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response 9,10,11,15,5.

Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms 9,10,11,15,5. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center 9,10,11,15,5.

Furthermore, H1 receptors are similar to muscarinic receptors 9,10,11,15,5. Consequently, diphenhydramine also acts as an antimuscarinic 9,10,11,15,5. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication 9,10,11,15,5.

Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties 9.

AHistamine H1 receptor
UMuscarinic acetylcholine receptor M2
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more

Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in approximately one hour 6,13. The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration 6,13.

Volume of distribution

Diphenhydramine is widely distributed throughout the body, including the CNS 16. Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range of 3.3 - 6.8 l/kg 16.

Protein binding

Some prescribing information records the protein binding of diphenhydramine as approximately 78% 16 while others have suggested the medication is about 80 to 85% 13 bound to plasma proteins.


Diphenhydramine undergoes rapid and extensive first-pass metabolism 16,13,8. In particular, two successive N-demethylations occur wherein diphenhydramine is demethylated to N-desmethyldiphenhydramine (the N-desmethyl metabolite) and then this metabolite is itself demethylated to N,N-didesmethyldiphenhydramine (the N,N-didesmethyl metabolite) 16,8. Subsequently, acetyl metabolites like N-acetyl-N-desmethyldiphenhydramine are generated via the amine moiety of the N,N-didesmethyl metabolite 8. Additionally, the N,N-didesmethyl metabolite also undergoes some oxidation to generate the diphenylmethoxyacetic acid metabolite as well 16,13,8. The remaining percentage of a dose of administered diphenhydramine is excreted unchanged 16,13,8. The metabolites are further conjugated with glycine and glutamine and excreted in urine 13.

Moreover, studies have determined that a variety of cytochrome P450 isoenzymes are involved in the N-demethylation that characterizes the primary metabolic pathway of diphenhydramine, including CYP2D6, CYP1A2, CYP2C9, and CYP2C19 7. In particular, CYP2D6 demonstrates higher affinity catalysis with the diphenhydramine substrate than the other isoenzymes identified 7. Consequently, inducers or inhibitors of these such CYP enzymes may potentially affect the serum concentration and incidence and/or severity of adverse effects associated with exposure to diphenhydramine 7.

Route of elimination

The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine 12,13. Only about 1% of a single dose is excreted unchanged in urine 12,13. The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites 12,13.

Half life

The elimination half-life ranges from 2.4-9.3 hours in healthy adults 16,13. The terminal elimination half-life is prolonged in liver cirrhosis 13.


Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in the range of 600-1300 ml/min 16.


Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others 10,11,12,13,16. Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes 13. Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse 13. Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow 16.

Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk 16. This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant 16.

Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults 16. Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects 13. Avoid use in elderly patients with confusion 13.

The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) 16.

After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease 16. However, the mean plasma clearance and apparent volume of distribution were not significantly affected 16.

LD50=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.

Affected organisms
  • Humans and other mammals
Diphenhydramine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Diphenhydramine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Diphenhydramine.
1,10-PhenanthrolineThe therapeutic efficacy of Diphenhydramine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Diphenhydramine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Diphenhydramine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Diphenhydramine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Diphenhydramine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Avoid alcohol.
  • Take with food.


Synthesis Reference

Alison B. Lukacsko, Joseph J. Piala, "Effect of a combination of a terbutaline, diphenhydramine and ranitidine composition on gastrointestinal injury produced by nonsteroidal anti-inflammatory compositions." U.S. Patent US5260333, issued December, 1983.

General References
  1. Raphael GD, Angello JT, Wu MM, Druce HM: Efficacy of diphenhydramine vs desloratadine and placebo in patients with moderate-to-severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2006 Apr;96(4):606-14. [PubMed:16680933]
  2. Abdi A, Rose E, Levine M: Diphenhydramine overdose with intraventricular conduction delay treated with hypertonic sodium bicarbonate and i.v. lipid emulsion. West J Emerg Med. 2014 Nov;15(7):855-8. doi: 10.5811/westjem.2014.8.23407. Epub 2014 Sep 19. [PubMed:25493135]
  3. Halpert AG, Olmstead MC, Beninger RJ: Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002 Jan;26(1):61-7. [PubMed:11835984]
  4. Jaju BP, Wang SC: Effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity of cat: a search for the locus of their antimotion sickness action. J Pharmacol Exp Ther. 1971 Mar;176(3):718-24. [PubMed:4329456]
  5. Flake ZA, Scalley RD, Bailey AG: Practical selection of antiemetics. Am Fam Physician. 2004 Mar 1;69(5):1169-74. [PubMed:15023018]
  6. Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97. [PubMed:2866055]
  7. Akutsu T, Kobayashi K, Sakurada K, Ikegaya H, Furihata T, Chiba K: Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos. 2007 Jan;35(1):72-8. doi: 10.1124/dmd.106.012088. Epub 2006 Oct 4. [PubMed:17020955]
  8. Rodrigues WC, Castro C, Catbagan P, Moore C, Wang G: Immunoassay screening of diphenhydramine (Benadryl(R)) in urine and blood using a newly developed assay. J Anal Toxicol. 2012 Mar;36(2):123-9. doi: 10.1093/jat/bkr015. [PubMed:22337782]
  9. StatPearls [Internet]: Diphenhydramine [Link]
  10. Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Tablets Patient Information [Link]
  11. Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Cream Monograph [Link]
  12. Electronic Medicines Compendium: Boots Sleepeaze (diphenhydramine hydrochloride) 50mg Tablets Monograph [Link]
  13. Electronic Medicines Compendium: Nytol One-A-Night (diphenhydramine hydrochloride) Monograph [Link]
  14. Diphenhydramine Hydrochloride Injection, USP FDA Label [File]
  15. DIPHENHYDRAMINE- diphenhydramine hcl tablet, coated DailyMed FDA Label [File]
  16. Benylin Chesty Coughs UK MHRA Product Information [File]
External Links
Human Metabolome Database
KEGG Compound
PubChem Compound
PubChem Substance
Therapeutic Targets Database
Guide to Pharmacology
GtP Drug Page
RxList Drug Page Drug Page
ATC Codes
D04AA32 — DiphenhydramineR06AA02 — DiphenhydramineD04AA33 — Diphenhydramine methylbromideR06AA52 — Diphenhydramine, combinations
AHFS Codes
  • 04:04.04 — Ethanolamine Derivatives
  • 04:04.00 — First Generation Antihistamines
PDB Entries
Download (73.5 KB)

Clinical Trials

Clinical Trials
0Not Yet RecruitingTreatmentAtopic Dermatitis (AD)1
0RecruitingDiagnosticStage IIB Esophageal Cancer / Stage IIB Esophageal Cancer AJCC v7 / Stage III Esophageal Cancer AJCC v7 / Stage IIIA Esophageal Cancer / Stage IIIA Esophageal Cancer AJCC v7 / Stage IIIB Esophageal Cancer / Stage IIIB Esophageal Cancer AJCC v7 / Stage IIIC Esophageal Cancer / Stage IIIC Esophageal Cancer AJCC v71
1Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Lymphocytic Leukaemia (CLL) / Non Hodgkin Lymphoma (NHL)1
1Active Not RecruitingTreatmentDiseases of Oesophagus Stomach and Duodenum1
1Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1CompletedNot AvailableAutonomic Failure / Idiopathic orthostatic hypotension1
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableTherapeutic Equivalence1
1CompletedBasic ScienceAllergic Rhinitis (AR)1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceNasal Congestion1
1CompletedDiagnosticPatients With Suspected Malignancies of the Pituitary Gland1
1CompletedTreatmentHealthy Volunteers4
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentPain NOS / Pharmacology, Clinical1
1CompletedTreatmentRestless Legs Syndrome (RLS)1
1CompletedTreatmentTumors, Solid1
1RecruitingDiagnosticA Diagnosis of Any Resectable Lung or Pleural Nodule1
1RecruitingTreatmentGraft Versus Host Disease (GVHD) / Sickle Cell Disorders1
1RecruitingTreatmentMetastatic Colorectal Cancers1
1RecruitingTreatmentNeoplasms Malignant1
1RecruitingTreatmentPompe's Disease1
1TerminatedNot AvailableHealthy Male Volunteers1
1TerminatedBasic ScienceDrug Metabolism, Poor, CYP2D6-RELATED1
1TerminatedTreatmentAlpha-1 Antitrypsin Deficiency1
1TerminatedTreatmentTransplantation, Liver1
1WithdrawnDiagnosticAbdominal Pain (AP) / Gallbladder disorders / Gallstone formation / Jaundice / Pancreatitis1
1, 2Active Not RecruitingTreatmentLung Cancers1
1, 2CompletedTreatmentKidney Diseases / Transplantation, Kidney1
1, 2CompletedTreatmentLeukemia, Acute Lymphocytic (ALL) / Leukemia, Acute Myelogenous (AML) / Leukemia, Chronic Myelogenous (CML) / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)1
1, 2CompletedTreatmentPost-Traumatic Headaches1
1, 2RecruitingTreatmentAdult Living Donor Kidney Transplant Recipients / Living Kidney Donors / Transplant, Kidney1
1, 2RecruitingTreatmentColorectal Cancers / Gastroesophageal Adenocarcinoma / Lung Cancer Non-Small Cell Cancer (NSCLC) / Transitional Cell Carcinoma / Tumors, Solid1
1, 2RecruitingTreatmentLiver Transplanted Patients / Living Donor (of the Respective Liver Transplant Recipient)1
1, 2TerminatedTreatmentColo-rectal Cancer / Colon/Rectal Cancer / Colon/Rectal Cancer Rectal Cancer / Rectal Carcinoma1
2Active Not RecruitingTreatmentAdvanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma / Non-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentRenal Cancers1
2Active Not RecruitingTreatmentSystemic Sclerosis-Associated PAH / Systemic Sclerosis-Associated Pulmonary Arterial Hypertension1
2CompletedNot AvailableMalignancies / Tumors, Solid1
2CompletedSupportive CareStomatitis, Aphthous1
2CompletedTreatmentBlood Cancers / Chronic Lymphocytic Leukaemia (CLL) / Graft Versus Host Disease (GVHD) / Hodgkins Disease (HD) / Leukemias / Malignancies / NHL / Smith-Magenis Syndrome1
2CompletedTreatmentBlood and Marrow Transplant (BMT) / Multiple Myeloma (MM) / Transplantation, Autologous / Transplantation, Homologous1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCerebrovascular Accident, Acute / Edema of the cerebrum1
2CompletedTreatmentChronic Idiopathic Urticaria1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentLeukemia, Mast-Cell / Mantle Cell Lymphoma (MCL)1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentNephritis, Lupus1
2CompletedTreatmentRejection, Transplant1
2CompletedTreatmentRenal Cell Adenocarcinoma1
2CompletedTreatmentRestless Legs Syndrome (RLS)1
2CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
2Not Yet RecruitingTreatmentDiabetic Macular Edema (DME)1
2Not Yet RecruitingTreatmentHigh Risk / Newly Diagnosed / Plasma Cell Myeloma1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2RecruitingTreatmentAlcohol Dependence1
2RecruitingTreatmentCocaine-Related Disorders1
2RecruitingTreatmentHNSCC / HPV-Related Squamous Cell Carcinoma1
2RecruitingTreatmentImpaired Renal Function / RrMM1
2RecruitingTreatmentTransplant, Kidney1
2TerminatedSupportive CareNausea / Unspecified Childhood Solid Tumor, Protocol Specific / Vomiting1
2TerminatedTreatmentBlood and Marrow Transplant (BMT) / Diffuse Large B-Cell / Lymphoma, B-Cell / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphomas: Non-Hodgkin / Malignant Lymphoma, Non-Hodgkin / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentHepatitis B Chronic Infection1
2TerminatedTreatmentProstate Cancer1
2TerminatedTreatmentT-cell Type Acute Leukemia-Precursor T-lymphoblastic Lymphoma/Leukaemia1
2TerminatedTreatmentTransplantation, Kidney1
2, 3CompletedTreatmentMalaria caused by Plasmodium falciparum1
2, 3CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
2, 3CompletedTreatmentVesicular Stomatitis1
2, 3TerminatedTreatmentSystemic Lupus Erythematosus (SLE)1
3Active Not RecruitingTreatmentPostoperative pain1
3CompletedTreatmentAcute Urticaria2
3CompletedTreatmentChronic Idiopathic Urticaria1
3CompletedTreatmentElective Caesarean Section Surgeries1
3CompletedTreatmentHeadaches / Intranasal Ketamine1
3CompletedTreatmentHealthy Volunteers1
3CompletedTreatmentNephritis, Lupus1
3Not Yet RecruitingTreatmentMalaria caused by Plasmodium falciparum1
3RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3RecruitingTreatmentPost-Traumatic Headaches1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentSleeplessness1
3WithdrawnTreatmentCoughing / Inflammatory Reaction / Rhinitis1
4Active Not RecruitingSupportive CareAdjunct Anesthesia Medication / Colonoscopy1
4CompletedDiagnosticAsthma Bronchial1
4CompletedPreventionHypnotic / Specified Sedative1
4CompletedTreatmentBacterial Infections1
4CompletedTreatmentCough Reflex Sensitivity1
4CompletedTreatmentMigraine / Nausea / Restlessness1
4CompletedTreatmentNasal Congestion1
4CompletedTreatmentExtra-pyramidal symptoms / Nausea1
4CompletedTreatmentNeurogenic Intermittent Claudication / Spinal Stenosis of Lumbar Region1
4CompletedTreatmentOccasional Sleeplessness1
4CompletedTreatmentSedation therapy1
4CompletedTreatmentTrigger Finger Disorder1
4Not Yet RecruitingOtherACL Injury1
4Not Yet RecruitingSupportive CareDiabetes Mellitus (DM)1
4Not Yet RecruitingTreatmentPrimary Total Hip Arthroplasty / Primary Total Knee Arthroplasty1
4RecruitingPreventionPremature Births1
Not AvailableActive Not RecruitingOtherPain NOS1
Not AvailableActive Not RecruitingScreeningAlcohol Dependence1
Not AvailableCompletedBasic ScienceHyperalgesia1
Not AvailableCompletedBasic ScienceMemory, Long-Term / Memory, Short-Term1
Not AvailableCompletedOtherPain, Neuropathic1
Not AvailableCompletedPreventionGeneral Surgery / Pain NOS1
Not AvailableCompletedPreventionHeadaches1
Not AvailableCompletedSupportive CareFocus of Study: Absorption of the Three Components in the Topical ABH Gel in Healthy Volunteers, and Determine if There Are Any Adverse Effects / Healthy Volunteers1
Not AvailableCompletedSupportive CareNausea / Vomiting1
Not AvailableCompletedTreatmentBenign Paroxysmal Positional Vertigo (BPPV)1
Not AvailableCompletedTreatmentEndometriosis1
Not AvailableCompletedTreatmentEndoscopy / Sedation therapy1
Not AvailableCompletedTreatmentHip Fracture Surgery / Post Operative Pain Control1
Not AvailableCompletedTreatmentItching1
Not AvailableCompletedTreatmentPain NOS1
Not AvailableRecruitingTreatmentAlcohol-Related Disorders / Brain Injury / Depression / Disease, Chronic / Mild Cognitive Impairment (MCI) / Pain NOS / Posttraumatic Stress Disorders / Quality of Life / Substance-Related Disorders / Suicidal Thoughts / Wounds and Injuries1
Not AvailableRecruitingTreatmentAnxiety Disorders / Moods Disorders / Pain Disorders / Somatization Disorder1
Not AvailableRecruitingTreatmentMigraine1
Not AvailableSuspendedDiagnosticBulimia Nervosa (BN) / Catechol-O-methyltransferase / Dopamine / Eating Disorders / Reward1
Not AvailableTerminatedNot AvailablePain, Chronic1
Not AvailableTerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableTerminatedTreatmentPrimary Headaches (Includes Migraines, Tension, Cluster Headaches)1
Not AvailableUnknown StatusSupportive CareEndoscopic Retrograde Cholangiopancreatography (ERCP) / Endoscopic Ultrasound (EUS)1
Not AvailableWithdrawnTreatmentPost Operative Nausea and Vomiting (PONV) / Rescue Emetic Therapy1


Not Available
  • Advance Pharmaceutical
  • Advent Pharmaceuticals Inc.
  • Amend
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • Auriga Pharmaceuticals LLC
  • Barr Pharmaceuticals
  • Baxter International Inc.
  • Bergen Brunswig
  • Bioniche Pharma
  • Bryant Ranch Prepack
  • C.O. Truxton Inc.
  • Cardinal Health
  • Carlisle Laboratories Inc.
  • Chattem Chemicals Inc.
  • Concord Labs
  • Consolidated Midland Corp.
  • Contract Pharm
  • CVS Pharmacy
  • Darby Dental Supply Co. Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • Equaline Vitamins
  • Fusion Pharmaceuticals LLC
  • General Injectables and Vaccines Inc.
  • GlaxoSmithKline Inc.
  • Goldline Laboratories Inc.
  • Group Health Cooperative
  • Hawthorn Pharmaceuticals
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Kraft Pharmaceutical Co. Inc.
  • Liberty Pharmaceuticals
  • Lnk International Inc.
  • Major Pharmaceuticals
  • Martin Surgical Supply
  • McNeil Laboratories
  • Medique Products
  • Medtech Labs
  • Merit Pharmaceuticals
  • Midlothian Labs
  • Mississippi State Dept Health
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nexgen Pharma Inc.
  • North Safety Products
  • Nucare Pharmaceuticals Inc.
  • Patient First Corp.
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Pfizer Inc.
  • Pharmaceutical Association
  • Pharmedix
  • Physicians Total Care Inc.
  • Poly Pharmaceuticals Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Procter & Gamble
  • Provident Pharmaceuticals LLC
  • Remedy Repack
  • Rite Aid Corp.
  • River's Edge Pharmaceuticals
  • Rugby Laboratories
  • Sandhills Packaging Inc.
  • Scientific Laboratories Inc.
  • Silarx Pharmaceuticals
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
  • Walgreen Co.
Dosage forms
Capsule; kitOral
CreamTopical20 mg/1mL
CreamTopical2.0 mL/100mL
LiquidOral12.5 mg/5mL
Capsule, gelatin coatedOral
PowderOral25 mg/1
LiquidOral12.5 mg
SolutionOral12.5 mg
GelTopical2 g/100g
CreamTopical2.0 %
Injection, solutionIntramuscular; Intravenous50 mg/1mL
TabletOral25 mg
Tablet, coatedOral25 mg/1
StripOral25 mg/1
Tablet, chewableOral12.5 mg
LiquidOral6.25 mg
CreamTopical2 %
ElixirOral12.5 mg
GelTopical20 mg/1mL
Tablet, chewableOral25 mg
GelTopical2 %
TabletOral25 mg/250mg
StripOral25 mg
Tablet, coatedOral25 mg/ 11
SyrupOral6.25 mg
TabletOral19 mg
SolutionOral6.25 mg
StripOral19 mg
TabletOral12.5 mg/1
Tablet, chewableOral12.5 mg/1
Kit; tabletOral
KitOral0.75 g/0.75g
KitOral0.86 g/0.86g
TabletOral38.0 mg
Capsule, coatedOral25 mg/1
Injection, solutionIntravenous50 mg/1mL
Capsule, liquid filledOral20 mg/1
TabletOral50 mg/1
LiquidIntravenous50 mg
Capsule25 mg/1
Capsule50 mg/1
CapsuleOral25 mg/1
CapsuleOral50 mg/1
Capsule, liquid filledOral50 mg/1
ElixirOral25 mg/10mL
InjectionIntramuscular50 mg/1mL
InjectionIntramuscular; Intravenous50 mg/1mL
InjectionParenteral50 mg/1mL
SolutionOral25 mg/10mL
SolutionOral50 mg/20mL
Tablet, film coatedOral25 mg/1
LiquidIntramuscular; Intravenous50 mg
Tablet, chewableOral
GelTopical2 mg/100mL
Capsule, liquid filledOral
Capsule, liquid filledOral25 mg/1
SolutionOral50 mg/40mL
Aerosol, sprayTopical
SolutionOral50 mg/30mL
LiquidTopical20.3 g/1L
SprayTopical2 g/100mL
GelTopical2.03 g/100g
StripOral12.5 mg
TabletOral12.5 mg
Tablet, orally disintegratingOral12.5 mg/1
LiquidOral50 mg/20mL
Capsule, gelatin coatedOral50 mg/1
LozengeOral25 mg
CapsuleOral25 mg
LiquidOral50 mg/30mL
SolutionOral50 mg
Tablet, film coatedOral50 mg/1
Capsule, liquid filledOral50 mg/21
TabletOral50 mg
Granule, for solutionOral
Tablet, coatedOral
ElixirOral2.5 mg
SolutionOral12.5 mg/5mL
SyrupOral12.5 mg/5mL
GelTopical20.5 mg/1mL
SolutionIntramuscular; Intravenous50 mg
GelTopical2 g/100mL
GelTopical.2 g/10mL
Tablet, coatedOral50 mg/1
Tablet, multilayerOral
Tablet, multilayer, extended releaseOral
GelTopical20 mg/1g
SprayTopical20 mg/1mL
Capsule, coatedOral
TabletOral25 mg/1
Tablet, film coatedOral
Tablet, delayed releaseOral
CapsuleOral50 mg
Tablet, chewableOral25 mg/1
Powder, for solutionOral
LiquidOral6.25 mg/1mL
LiquidOral25 mg/10mL
Capsule, gelatin coatedOral50 mg/21
SprayTopical2.0 %
LiquidOral50 mg
Capsule, gelatin coatedOral25 mg/1
Unit descriptionCostUnit
DiphenhydrAMINE HCl 100 50 mg capsule Bottle13.99USD bottle
Diphenhydramine 50 mg/ml3.94USD ml
Diphenhydramine 50 mg/ml vial1.69USD ml
DiphenhydrAMINE HCl 50 mg/ml vial1.44USD vial
Dytan 25 mg tablet chewable1.37USD tablet
Benadryl 50 mg/ml vial1.36USD ml
Diphenmax 25 mg tablet1.24USD tablet
Benadryl allergy 25 mg strips0.45USD strip
Unisom sleep aid tablet0.34USD tablet
Sleep-eze 3 tablet0.29USD tablet
Compoz 50 mg tablet0.27USD tablet
Sominex max str 50 mg caplet0.27USD caplet
Benadryl allergy fastmelt tablet0.26USD tablet
Unisom 25 mg sleeptabs0.25USD tablet
Unisom 50 mg sleepgels0.25USD each
Unisom sleepmelts 25 mg tablet0.24USD tablet
Nytol 25 mg tablet0.23USD tablet
Benadryl allergy-sinus caplet0.22USD caplet
Compoz 25 mg gelcap0.2USD capsule
Benadryl allergy 25 mg softgel0.19USD softgel capsule
Benadryl allergy 25 mg ultratab0.19USD tablet
Benadryl allergy-cold kapgels0.19USD each
Benadryl allergy-sinus kapgels0.19USD each
Benadryl-d allergy-sinus ultratab0.19USD tablet
Diphenhydramine hcl powder0.17USD g
Eql allergy 25 mg tablet0.17USD tablet
Nighttime sleep aid 25 mg cplt0.17USD caplet
Banophen anti-itch 2% cream0.16USD g
Benadryl itch relief stick0.16USD ml
Sominex 25 mg tablet0.16USD tablet
Benadryl allergy 25 mg kapgels0.15USD each
Allergy 25 mg tablet0.14USD tablet
Benadryl 25 mg kapseals0.14USD each
Benadryl itch stopping crm0.14USD g
DiphenhydrAMINE HCl 25 mg capsule0.13USD capsule
Diphenhist with zinc cream0.12USD g
Ra allergy 25 mg tablet0.12USD tablet
CVS Pharmacy allergy 25 mg tablet0.11USD tablet
Diphenhydramine 25 mg minitab0.11USD tablet
Simply sleep 25 mg caplet0.11USD caplet
Sleep ii tablet0.11USD tablet
Diphenhydramine 50 mg capsule0.1USD capsule
Benadryl 2% spray0.09USD ml
Diphenhist 50 mg tablet0.09USD tablet
Genahist 25 mg tablet0.09USD tablet
Ra sleep tablet0.09USD tablet
Banophen 25 mg tablet0.08USD tablet
Wal-dryl anti-itch spray0.08USD ml
CVS Pharmacy allergy 25 mg caplet0.07USD caplet
Nighttime sleep aid 25 mg caplet0.07USD caplet
CVS Pharmacy itch relief spray0.06USD ml
Diphen 25 mg capsule0.06USD capsule
Diphenhist 25 mg caplet0.06USD caplet
Benadryl anti-itch 0.45% gel0.05USD g
Diphenhydramine 50 mg caplet0.05USD caplet
Benadryl itch stopping gel0.04USD g
Child benadryl-d aller-sin liquid0.04USD ml
Diphenhydramine 25 mg capsule0.04USD capsule
Vicks 44d cough & head liquid0.03USD ml
Vicks 44e cough & chest liquid0.03USD ml
Banophen allergy liquid0.02USD ml
Diphenhydramine 25 mg tablet0.02USD tablet
Ra anti-tussive dm syrup0.02USD ml
Siladryl 12.5 mg/5 ml liquid0.02USD ml
Silphen cough syrup0.02USD ml
Silphen dm cough syrup0.02USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patent NumberPediatric ExtensionApprovedExpires (estimated)
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more


Experimental Properties
melting point (°C)161-162Martin, H., Hafliger, F.,Gatzi, K.and Grob, A.; U.S. Patent 2,397,799; April 2,1946; assigned to J.R. Geigy AG, Switzerland. Rieveschl, G. Jr.; U.S. Patent 2,421,714; June 3,1947; assigned to Parke, Davis & Co. Rieveschl, G. Jr.; U.S. Patent 2,427,878; September 23,1947; assigned to Parke, Davis & Company.
boiling point (°C)150-165 °C at 2.00E+00 mm HgPhysProp
water solubility3060 mg/L (at 37 °C)BEILSTEIN
logP3.27HANSCH,C ET AL. (1995)
pKa8.98SANGSTER (1994)
Predicted Properties
Water Solubility0.0752 mg/mLALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity79.93 m3·mol-1ChemAxon
Polarizability29.86 Å3ChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Human Intestinal Absorption+0.9898
Blood Brain Barrier+0.9381
Caco-2 permeable+0.8744
P-glycoprotein substrateSubstrate0.6211
P-glycoprotein inhibitor INon-inhibitor0.6632
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterInhibitor0.7752
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.6173
CYP450 1A2 substrateInhibitor0.8306
CYP450 2C9 inhibitorNon-inhibitor0.9144
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9039
CYP450 3A4 inhibitorNon-inhibitor0.934
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7293
Ames testNon AMES toxic0.9132
BiodegradationNot ready biodegradable0.9253
Rat acute toxicity2.7846 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.536
hERG inhibition (predictor II)Inhibitor0.6318
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-9100000000-7b9eb1f702c76f6b6062
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-9200000000-b9014c8fc8ccbba24163
MS/MS Spectrum - Quattro_QQQ 10V, N/ALC-MS/MSsplash10-0006-0090000000-a71e531b49571f09ab25
MS/MS Spectrum - Quattro_QQQ 25V, N/ALC-MS/MSsplash10-00kk-0980000000-cce91896f34562beeffa
MS/MS Spectrum - Quattro_QQQ 40V, N/ALC-MS/MSsplash10-001i-1900000000-4c29bd5e0eab94596eaa
MS/MS Spectrum - EI-B (Unknown) , PositiveLC-MS/MSsplash10-0a4i-9100000000-ab642e8f86de11af896c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000t-0910000000-3576ca5ec77ab87354ec
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-0ccd6de9ca58593fd490
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-3568aae4c27ffe333c0e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-22e0c745355c836f1535
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-6bb69a66a343440c64f8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-1b87d83415d22bb17f1b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gb9-0900000000-50251362d768cd1b1c4f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gb9-0900000000-9f37a733a05f5b01d313
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-7d73b95ed09ea2d72260
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gb9-2900000000-1666a8ab5a6d81c0bd01
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-3f31841d858381760f03
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-de872e048c7e12cef490
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-de872e048c7e12cef490
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0900000000-789a4a3fe118d5bf2456
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-2900000000-8ef94659f614b9ff24ca
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-2950000000-7c7a9841f2f0b6428d69
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable


This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Organic compounds
Super Class
Benzene and substituted derivatives
Sub Class
Direct Parent
Alternative Parents
Benzylethers / Trialkylamines / Dialkyl ethers / Organopnictogen compounds / Hydrocarbon derivatives
Diphenylmethane / Benzylether / Tertiary aliphatic amine / Tertiary amine / Ether / Dialkyl ether / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, ether (CHEBI:4636) / a small molecule (CPD-10890)


1. Histamine H1 receptor
Pharmacological action
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
Uniprot ID
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Piao H, Nagai S, Tsurumaki T, Niki T, Higuchi H: Potentiation by neuropeptide Y of histamine H1 receptor-mediated contraction in rat blood vessels. Vascul Pharmacol. 2007 Apr;46(4):260-70. Epub 2006 Oct 27. [PubMed:17169617]
  3. Kesiova M, Alexandrova A, Yordanova N, Kirkova M, Todorov S: Effects of diphenhydramine and famotidine on lipid peroxidation and activities of antioxidant enzymes in different rat tissues. Pharmacol Rep. 2006 Mar-Apr;58(2):221-8. [PubMed:16702624]
  4. Hasala H, Moilanen E, Janka-Junttila M, Giembycz MA, Kankaanranta H: First-generation antihistamines diphenhydramine and chlorpheniramine reverse cytokine-afforded eosinophil survival by enhancing apoptosis. Allergy Asthma Proc. 2007 Jan-Feb;28(1):79-86. [PubMed:17390763]
  5. Wang Z, Woolverton WL: Self-administration of cocaine-antihistamine combinations: super-additive reinforcing effects. Eur J Pharmacol. 2007 Feb 28;557(2-3):159-60. Epub 2006 Dec 1. [PubMed:17196194]
  6. Ishikawa T, Takechi K, Rahman A, Ago J, Matsumoto N, Murakami A, Kamei C: Influences of histamine H1 receptor antagonists on maximal electroshock seizure in infant rats. Biol Pharm Bull. 2007 Mar;30(3):477-80. [PubMed:17329841]
  7. Havas TE, Cole P, Parker L, Oprysk D, Ayiomamitis A: The effects of combined H1 and H2 histamine antagonists on alterations in nasal airflow resistance induced by topical histamine provocation. J Allergy Clin Immunol. 1986 Nov;78(5 Pt 1):856-60. [PubMed:2878016]
Pharmacological action
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
Uniprot ID
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
  1. Liu H, Zheng Q, Farley JM: Antimuscarinic actions of antihistamines on the heart. J Biomed Sci. 2006 May;13(3):395-401. [PubMed:16453179]


Pharmacological action
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
Uniprot ID
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
  1. Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J: In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos. 1998 Jun;26(6):536-9. [PubMed:9616188]
  2. Akutsu T, Kobayashi K, Sakurada K, Ikegaya H, Furihata T, Chiba K: Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos. 2007 Jan;35(1):72-8. doi: 10.1124/dmd.106.012088. Epub 2006 Oct 4. [PubMed:17020955]
  3. Lessard E, Yessine MA, Hamelin BA, Gauvin C, Labbe L, O'Hara G, LeBlanc J, Turgeon J: Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. J Clin Psychopharmacol. 2001 Apr;21(2):175-84. [PubMed:11270914]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Pharmacological action
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
Uniprot ID
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Connecticut's Official State Website: CYP Chart [File]
Pharmacological action
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
Uniprot ID
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Pharmacological action
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
Uniprot ID
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]


Pharmacological action
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
Uniprot ID
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
  1. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]
Pharmacological action
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
Uniprot ID
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
  1. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [PubMed:11160873]

Drug created on June 13, 2005 07:24 / Updated on August 21, 2019 23:42